4 research outputs found
Insertable Fast-Response Amperometric NO/CO Dual Microsensor: Study of Neurovascular Coupling During Acutely Induced Seizures of Rat Brain Cortex
This paper reports the fabrication
of an insertable amperometric
dual microsensor and its application for the simultaneous and fast
sensing of NO and CO during acutely induced seizures of living rat
brain cortex. NO and CO are important signaling mediators, controlling
cerebrovascular tone. The dual NO/CO sensor is prepared based on a
dual microelectrode having Au-deposited Pt microdisk (WE1, 76 μm
diameter) and Pt black-deposited Pt disk (WE2, 50 μm diameter).
The different deposited metals for WE1 and WE2 allow the selective
anodic detection of CO at WE1 (+0.2 V vs Ag/AgCl) and that of NO at
WE2 (+0.75 V vs Ag/AgCl) with sufficient sensitivity. Fluorinated
xerogel coating on this dual electrode provides exclusive selectivity
over common biological interferents, along with fast response time.
The miniaturized size (end plane diameter < 300 μm) and tapered
needle-like sensor geometry make the sensor become insertable into
biological tissues. The sensor is applied to simultaneously monitor
dynamic changes of NO and CO levels in a living rat brain under acute
seizure condition induced by 4-aminopyridine in cortical tissue near
the area of seizure induction. In-tissue measurement shows clearly
defined patterns of NO/CO changes, directly correlated with observed
LFP signal. Current study verifies the feasibility of a newly developed
NO/CO dual sensor for real-time fast monitoring of intimately connected
NO and CO dynamics
Dual Electrochemical Microsensor for Real-Time Simultaneous Monitoring of Nitric Oxide and Potassium Ion Changes in a Rat Brain during Spontaneous Neocortical Epileptic Seizure
In
this work, we developed a dual amperometric/potentiometric microsensor
for sensing nitric oxide (NO) and potassium ion (K<sup>+</sup>). The
dual NO/K<sup>+</sup> sensor was prepared based on a dual recessed
electrode possessing Pt (diameter, 50 μm) and Ag (diameter,
76.2 μm) microdisks. The Pt disk surface (WE1) was modified
with electroplatinization and the following coating with fluorinated
xerogel; and the Ag disk surface (WE2) was oxidized to AgCl on which
K<sup>+</sup> ion selective membrane was loaded subsequent to the
silanization. WE1 and WE2 of a dual microsensor were used for amperometric
sensing of NO (106 ± 28 pA μM<sup>–1</sup>, <i>n</i> = 10, at +0.85 V applied vs Ag/AgCl) and for potentiometric
sensing of K<sup>+</sup> (51.6 ± 1.9 mV pK<sup>–1</sup>, <i>n</i> = 10), respectively, with high sensitivity.
In addition, the sensor showed good selectivity over common biological
interferents, sufficiently fast response time and relevant stability
(within 6 h in vivo experiment). The sensor had a small dimension
(end plane diameter, 428 ± 97 μm, <i>n</i> =
20) and needle-like sharp geometry which allowed the sensor to be
inserted in biological tissues. Taking advantage of this insertability,
the sensor was applied for the simultaneous monitoring of NO and K<sup>+</sup> changes in a living rat brain cortex at a depth of 1.19 ±
0.039 mm and near the spontaneous epileptic seizure focus. The seizures
were induced with 4-aminopyridine injection onto the rat brain cortex.
NO and K<sup>+</sup> levels were dynamically changed in clear correlation
with the electrophysiological recording of seizures. This indicates
that the dual NO/K<sup>+</sup> sensor’s measurements well reflect
membrane potential changes of neurons and associated cellular components
of neurovascular coupling. The newly developed NO/K<sup>+</sup> dual
microsensor showed the feasibility of real-time fast monitoring of
dynamic changes of closely linked NO and K<sup>+</sup> in vivo
Flexible, Transparent, and Noncytotoxic Graphene Electric Field Stimulator for Effective Cerebral Blood Volume Enhancement
Enhancing cerebral blood volume (CBV) of a targeted area without causing side effects is a primary strategy for treating cerebral hypoperfusion. Here, we report a new nonpharmaceutical and nonvascular surgical method to increase CBV. A flexible, transparent, and skin-like biocompatible graphene electrical field stimulator was placed directly onto the cortical brain, and a noncontact electric field was applied at a specific local blood vessel. Effective CBV increases in the blood vessels of mouse brains were directly observed from <i>in vivo</i> optical recordings of intrinsic signal imaging. The CBV was significantly increased in arteries of the stimulated area, but neither tissue damage nor unnecessary neuronal activation was observed. No transient hypoxia was observed. This technique provides a new method to treat cerebral blood circulation deficiencies at local vessels and can be applied to brain regeneration and rehabilitation
Intracellularly Activatable Nanovasodilators To Enhance Passive Cancer Targeting Regime
Conventional cancer targeting with
nanoparticles has been based
on the assumed enhanced permeability and retention (EPR) effect. The
data obtained in clinical trials to date, however, have rarely supported
the presence of such an effect. To address this challenge, we formulated
intracellular nitric oxide-generating nanoparticles (NO-NPs) for the
tumor site-specific delivery of NO, a well-known vasodilator, with
the intention of boosting EPR. These nanoparticles are self-assembled
under aqueous conditions from amphiphilic copolymers of polyÂ(ethylene
glycol) and nitrated dextran, which possesses inherent NO release
properties in the reductive environment of cancer cells. After systemic
administration of the NO-NPs, we quantitatively assessed and visualized
increased tumor blood flow as well as enhanced vascular permeability
than could be achieved without NO. Additionally, we prepared doxorubicin
(DOX)-encapsulated NO-NPs and demonstrated consequential improvement
in therapeutic efficacy over the control groups with considerably
improved DOX intratumoral accumulation. Overall, this proof of concept
study implies a high potency of the NO-NPs as an EPR enhancer to achieve
better clinical outcomes